Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S525-S526 ◽  
Author(s):  
L.C. Del Sant ◽  
E. Magalhães ◽  
A.C. Lucchese ◽  
H.N. Palhares Alves ◽  
L.M. Sarin ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Receptor Antagonist ◽  
Clinical Characteristics ◽  
Treatment Resistant Depression ◽  
Antidepressant Response ◽  
Treatment Resistant ◽  
Clinical Predictors ◽  
Post Infusion ◽  
History Of ◽  
Resistant Depression

IntroductionThe non-competitive N-methyl-d-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in treatment-resistant depression (TRD). However, only a few studies have investigated which clinical characteristics predict a response to ketamine.ObjectivesTo assess sociodemographic variables and clinical markers that predict response to ketamine in unipolar TRD patients.MethodsSearches of Pubmed, NCBI and Google Scholar were conducted for clinical trials and systematic reviews, through October 2016, using the keywords:ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, clinical predictors.ResultsFindings support the following clinical predictors:– sociodemographic variables: positive family history of alcohol abuse disorder in first-degree relative (increased antidepressant response and fewer depressive symptoms for up to 4 weeks post-infusions), higher BMI (improvement in depression severity at 230 minutes and one day post-infusion), negative history of suicide attempt (greater improvement at day 7);– infusion-associated events: greater dissociation during infusion (better antidepressant response at 230 minutes and one week post-infusion); rapid response to first infusion (sustained response to subsequent infusions in one-third responders for up to 83 days);– symptomatology: anxious depression (fewer depression symptoms at day one up to 25 associated with longer time to relapse); neurocognitive performance (lower attention) predicts change in severity of depressive symptoms over six infusions.ConclusionsFindings suggest that specific clinical characteristics are predictors of ketamine response in TRD. Future studies confirming reliable predictors will assist clinicians to implement efficacious and individualized treatment for TRD patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

2021 ◽  
Author(s):  
Joshua S. Siegel ◽  
Ben J. A. Palanca ◽  
Beau M. Ances ◽  
Evan D. Kharasch ◽  
Julie A. Schweiger ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Limbic System ◽  
Anterior Cingulate ◽  
Sustained Remission ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Subgenual Anterior Cingulate Cortex ◽  
Post Infusion ◽  
Resistant Depression

AbstractKetamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

2021 ◽  
Vol 35 (2) ◽  
pp. 142-149
Author(s):  
Ana C Lucchese ◽  
Luciana M Sarin ◽  
Eduardo J Muniz Magalhães ◽  
Lorena C Del Sant ◽  
Camila B Puertas ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Anxiety Disorder ◽  
Rating Scale ◽  
Treatment Algorithm ◽  
Treatment Resistance ◽  
Antidepressant Effect ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Clinical Predictors ◽  
Resistant Depression

Background: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. Results: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

2021 ◽  
Author(s):  
Mu-Hong Chen ◽  
Wei-Chen Lin ◽  
Cheng-Ta Li ◽  
Shih-Jen Tsai ◽  
Hui-Ju Wu ◽  
...  
Keyword(s):  
Working Memory ◽  
Depressive Symptoms ◽  
Treatment Response ◽  
Low Dose ◽  
Memory Function ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Ketamine Infusion ◽  
Treatment Groups ◽  
Resistant Depression

Abstract Introduction Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. Methods A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. Results A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. Discussion An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

A pilot, open study of sertraline in outpatients with treatment-resistant depression (TRD) or with a history of TRD who responded but later relapsed

2003 ◽  
Vol 18 (5) ◽  
pp. 293-296
Author(s):  
George I. Papakostas ◽  
Timothy Petersen ◽  
John J. Worthington ◽  
Pamela A. Roffi ◽  
Jonathan E. Alpert ◽  
...  
Keyword(s):  
Open Study ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
History Of ◽  
Resistant Depression

Toward Optimal Treatments for Major Depression

CNS Spectrums ◽  
2002 ◽  
Vol 7 (2) ◽  
pp. 148-154 ◽  
Author(s):  
Pierre Blier ◽  
Herbert Ward
Keyword(s):  
Major Depression ◽  
Therapeutic Response ◽  
Antidepressant Drug ◽  
Treatment Resistant Depression ◽  
Antidepressant Response ◽  
Controlled Clinical Trials ◽  
Treatment Resistant ◽  
Ongoing Research ◽  
Resistant Depression ◽  
First And Second Generation

ABSTRACTThe treatment of major depression remains problematic for several reasons. In particular, the therapeutic response to medications usually does not manifest itself until a week after administration has begun, and more than half the patients will not experience a full recovery with the first antidepressant drug administration. There are, however, some pharmacologic strategies that can accelerate antidepressant response. When facing a treatment-resistant depression, combination therapy offers a more time-efficient approach to achieve remission than drug substitution. These interventions have been devised on a better understanding of the basis for the therapeutic response obtained with the first- and second-generation antidepressants, and evidence derived from controlled clinical trials of their superior effectiveness is growing. The rationale for such approaches will be described in this article, as well as their advantages and potential inconveniences. Ongoing research in this field continues to fuel the development of novel, better-tolerated, and more effective pharmacotherapies for depression.

scholarly journals 118 Use of Patient Health Questionnaire to Predict Relapses in Patients with Treatment-resistant Depression Treated With Esketamine + Oral Antidepressant

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 276-277
Author(s):  
Carol Jamieson ◽  
Nan Li ◽  
Ella Daly ◽  
Adam Janik ◽  
Rosanne Lane ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Patient Health Questionnaire ◽  
Controlled Study ◽  
Health Questionnaire ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Relapse Risk ◽  
Total Score Range ◽  
Patient Health ◽  
Resistant Depression

Abstract:Objective:To assess the Patient Health Questionnaire (PHQ-9) as a predictor of relapse of depressive symptoms in treatment-resistant depression (TRD).Method:Analysis included maintenance phase data from SUSTAIN-1 (NCT02493868), a randomized, double-blind, active-controlled study in TRD patients that evaluated efficacy of intranasal esketamine (ESK) + oral antidepressant (AD) vs AD + intranasal placebo in delaying relapse of depressive symptoms. A ≥50% reduction in initial symptom score and total score of ≤12 were considered as response and remission, respectively, using the Montgomery-Asberg Depression Rating Scale. PHQ-9 total score (range, 0–27), PHQ-2 total score (0–6), and individual items of the PHQ-9 (0–3) were examined as predictors of relapse. Data were collected every 2 weeks. Association between time-varying PHQ-9 and event of depression relapse was evaluated in Andersen-Gill Cox model.Results:Of 176 stable remitters, 63 had a relapse event (ESK+AD [n=24]; AD+placebo [n=39]). Of 121 stable responders, 50 had a relapse event (ESK+AD [n=16]; AD+placebo [n=34]). Among stable remitters, PHQ-9 total score (HR; 95% CI [1.12; 1.04–1.21]) and PHQ-2 total score (1.58; 1.25–1.99) were associated with relapse risk. PHQ-9 items #1 (loss of pleasure, 2.07; 1.38–3.09), #2 (feeling down, 2.18; 1.51–3.15), #4 (feeling tired, 1.54; 1.13–2.11), and #6 (negative self-view, 2.27; 1.41–3.66) were associated with relapse risk. PHQ-2 total scale yielded the smallest Akaike’s Information Criterion among stable remitters and responders.Conclusion:PHQ-9, PHQ-2 total scores or individual items may be useful for predicting relapse of depressive symptoms among stable TRD patients.Funding Acknowledgements:This study was sponsored by Janssen Research and Development, LLC.

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